The goal of the proposed research plan is to clarify the intrarenal neural pathways involved in autonomic control of renin secretion. It is known that renin secretion rate can be increased by neural stimulation of intrarenal beta-adrenoceptors. Evidence from this laboratory suggests that the renal nerves also stimulate renin secretion by activation of intrarenal alpha-adrenoceptors. In addition, the kidney contains acetylcholinesterase-staining fibers; these may be parasympathetic postganglionic nerves. The ability of intrarenal alpha-adrenoceptors to mediate increased renin release will be studied in pentobarbital-anesthetized dogs by renal artery infusion of alpha-adrenergic agonists and tyramine, before and after intrarenal alpha-adrenergic blockade. Multiple agonist dosages selected on the basis of their effects on renal vascular resistance, glomerular filtration rate and urinary sodium excretion will be studied. The presence of a vagal innervation of the kidney will be tested neurophysiologically, and if confirmed, the effect of posterior vegal nerve stimulation on renin release will be studied. A possible role for renal cholinergic nerves in control of renin release will be evaluated by vagal or renal nerve stimulation, and by renal artery infusion of acetylcholine, before and after intrarenal muscarinic blockade.